This Program Project is concerned with three parasitic diseases, schistosomiasis, leishmaniasis and malaria, that are major health problems in Brazil. The projects are in Amazonas, Bahia, and Ceara. Three themes tie them together. The first is the development and application of new diagnostic tools and their application in epidemiologic studies to determine risk factors needed to plan rational control schemes; kDNA probes, monoclonal antibodies, purified antigens and fusion proteins are being used. The epidemiology project in Amazonas, unique in its design and scope, is concerned with the spread of cutaneous leishmaniasis in Cidade Nova, a new development adjacent to the forest. Another study, in Ceara, concerns an explosive outbreak of cutaneous leishmaniasis where cases are appearing in clusters and the clinical picture suggests some visceralization. The second theme is the development of immunotherapy and vaccines. in Amazonas, an immunotherapy trial comparing a mixture of BCG and killed L.b. guyanensis with Glucantime therapy is planned (in collaboration with Dr. Convit); the production of monoclonal antibodies against snake venoms for immunotherapy of snakebites will be initiated. In Bahia, persons with schistosomiasis thought to be immune will be tested to determine if they are more reactive to protective antigens and fusion proteins than susceptible persons. Human T and B cell hybridomas are being produced to identify reactive epitopes on protective schistosome antigens. The third theme tying the projects together is the delineation of mechanisms of immunopathology and immunity. The presence of leishmania antigen will be sought in mucocutaneous leishmanial lesions to investigate the hypothesis that the chronic inflammatory reaction there is driven by delayed hypersensitivity to antigens in the lesion. The mechanisms of the immune modulating effect of schistosome antigens in mother's milk will be studied. All of this work is an extension of previous collaborative studies between American and Brazilian scientists and should continue to be of mutual benefit.